Allogeneic transplantation of bone marrow and lymph node cells matched to the host at major histocompatibility loci, but disparate at minor loci, can generate a severe graft-vs-host disease (GVHD). In M1s disparate transplants, selective expansion of elements of the splenic T cell receptor V-beta repertoire indicated that M1s reactivity might play an important role in early GVHD. After transplantation of BALB/c (H-2d, M1s-c) cells into irradiated DBA/2 (H-2d, M1s-a) hosts, 65% of the CD4 and 29% of the CD8 splenic T cells expressed the M1s(a)-reactive V-beta6 and V-beta8.1 T cell receptors (compared with 16% and 7% respectively in syngeneic BALC/c transplants). To assess the dependence of GVHD on M1s- reactivity, V-beta6 and V-beta8.1,2 expressing T cells were removed from the BALB/c donor inocula by antibody and magnetic bead treatment prior to injection into DBA/2 hosts. 90% of BALB/c--->DBA/2 mice died at 3-5 weeks after undepleted transplants, but greater than 70% survived at 12 weeks after V-beta depleted transplants. BALB/c--->C57BL/6 grafts (H-2 disparity) produced a marked expansion of donor T cells, but no selective expansion of V-beta6 or V-beta8.1. C57BL/6 hosts died at 6-10 days, whether or not the donor BALB/c V-beta6 and V-beta8.1,2 subsets had been depleted. The mechanism(s) responsible from immune protection of mice to the intracellular parasite Toxoplasma gondii was studied. Immunization with a temperature sensitive mutant resulted in priming such that CD4+ and CD8+ spleen cells responded in vitro to T. gondii antigens by IL-2 and INF-gamma production and CD8+ cells generated antigen-specific H-2 restricted cytotoxic T lymphocytes. CD8+ but not CD4+ T cells were crucial for protective immunity in immunized mice. Chronic T. gondii infection in F1 mice preceded the induction of chronic or acute parent- int-F1 GVHR. Acute GVHR resulted in T. gondii brain cysts and death, whereas chronic GVHR mice survived the infection.